Inverse relationship between obesity and FTO gene expression in visceral adipose tissue in humans

Aims/hypothesis Recently, FTO was identified as a candidate gene contributing to both childhood and severe adult obesity. We tested the hypothesis that mRNA expression of FTO and/or of the neighbouring RPGRIP1L in adipose tissue correlates with measures of obesity and fat distribution. We also investigated whether the FTO obesity risk alleles might explain variability in FTO and RPGRIP1L mRNA expression. Methods In paired samples of visceral and subcutaneous adipose tissue from 55 lean and obese participants, we investigated whether FTO and RPGRIP1L mRNA expression is fat depot-specific, altered in obesity and related to measures of fat accumulation, insulin sensitivity and glucose metabolism. All participants were genotyped for the obesity-associated rs8050136 FTO variant. Results FTO mRNA expression was threefold higher in subcutaneous than in visceral adipose tissue. Subcutaneous FTO expression correlated with visceral FTO expression. FTO gene expression in both depots correlated with age and was negatively correlated to BMI and per cent body fat. FTO mRNA levels were not related to measures of insulin sensitivity and glucose metabolism. RPGRIP1L mRNA expression was 1.6-fold higher in visceral than in subcutaneous adipose tissue, but did not correlate with anthropometric and metabolic characteristics. There was no association between rs8050136 and FTO or RPGRIP1L mRNA expression in adipose tissue. Conclusions/interpretation Expression of adipose tissue FTO mRNA is fat depot-specific and negatively correlates with measures of obesity. However, the direction of this relationship still needs to be elucidated.